Circulating KL-6, a biomarker of lung injury, in obstructive sleep apnoea.

In obstructive sleep apnoea (OSA), oxidative stress contributes to endothelial dysfunction in the peripheral circulation. In the lung, oxidative stress can lead to alveolar injury. The present authors hypothesised that patients with OSA would have biomarker evidence of increased alveolar wall permeability. Sleep characteristics, brachial artery flow-mediated dilation and plasma KL-6 levels were observed in 11 otherwise healthy patients with OSA and 10 controls. Median (interquartile range) plasma KL-6 levels were higher in patients with OSA compared with controls: 317 (232-506) U.mL(-1) versus 226 (179-257) U.mL(-1), respectively. Higher plasma KL-6 levels were associated with greater time spent asleep with an oxyhaemoglobin saturation <90%, lower nadir saturation, more frequent desaturation of >4% during sleep and lower brachial artery flow-mediated dilation. Adjustment for nadir saturation or flow-mediated dilation attenuated the association between plasma KL-6 levels and OSA. Circulating KL-6 levels are elevated in some patients with obstructive sleep apnoea, possibly reflecting increased alveolar wall permeability.

Accuracy of an interferon-gamma release assay to detect active pulmonary and extra-pulmonary tuberculosis.

OBJECTIVE: To examine the performance of an interferon-gamma (IFN-gamma) release assay (QuantiFERON-TB 2G assay [QFT-G]) to detect Mycobacterium tuberculosis infection in a Japanese general hospital, for the diagnosis of active pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB). DESIGN: We prospectively examined the performance of QFT-G in 194 patients suspected of active TB. Diagnosis was confirmed by 1) positive M. tuberculosis cultures, or 2) clinical manifestations or laboratory or pathological findings consistent with active TB and response to specific therapy. RESULTS: Three patients with indeterminate QFT-G results were excluded. Among the remaining 191 patients, 77 had active TB. When the cut-off concentration of IFN-gamma was set at 0.35 IU/ml, as recommended by the manufacturer, the assay was positive in 69 patients and negative in 122. The sensitivity of the assay was 76.6% in all patients, 74.5% in the 47 patients with PTB and 80.0% in the 30 patients with EPTB. The overall specificity of the assay was 91.2%. CONCLUSION: Although the specificity of the QFT-G to detect active TB was high and its sensitivity low, it was as accurate for the detection of active EPTB as for PTB when the 0.35 IU/ml INF-gamma cut-off concentration was used.

Neutrophil elastase inhibitor improves postoperative clinical courses after thoracic esophagectomy.

Sivelestat sodium hydrate is a selective inhibitor of neutrophil elastase (NE), and is effective in acute lung injury associated with systemic inflammatory response syndrome (SIRS). The effect of Sivelestat for postoperative clinical courses after transthoracic esophagectomy was investigated. Consecutive patients with carcinoma of the thoracic esophagus who underwent transthoracic esophagectomy between 2003 and 2004 were assigned to the Sivelestat-treated group (n = 18), and those between 1998 and 2003 were assigned to the control group (n = 25). The morbidity rate, duration of postoperative SIRS, mechanical ventilation, and intensive care unit (ICU) stay, and the sum of the sequential organ failure assessment scores at all time points after the operation were compared. Serum NE activities and serum concentrations of TNF-alpha, IL-1beta, IL-6, and high mobility group box chromosomal protein 1 (HMGB1) were measured. Postoperative complications developed in three patients in the control group, and one in the Sivelestat-treated group. The durations of SIRS, mechanical ventilation, and ICU stay were significantly shorter in the Sivelestat-treated group. Even in patients without complications, the durations of mechanical ventilation, and ICU stay were also significantly shorter, and the arterial oxygen pressure/fraction of inspired oxygen ratio at postoperative day 1 was significantly higher in the Sivelestat-treated group. Serum NE activities and serum concentrations of IL-1beta, IL-6, and HMGB1 were significantly suppressed in the Sivelestat-treated group. Postoperative Sivelestat treatment after transthoracic esophagectomy improves the condition of SIRS and postoperative clinical courses, even in patients without complications.

Role of Toll-like receptor 4 in hyperoxia-induced lung inflammation in mice.

OBJECTIVE: Prolonged exposure to hyperoxia causes lung inflammation, but the role of Toll-like receptor 4 (TLR4) in hyperoxia-induced signal transduction remains unclear. MATERIAL OR SUBJECTS: We evaluated neutrophil accumulation, signal transduction and cytokine production during hyperoxia, comparing TLR4 mutant (C3H/HeJ) and wild type (C3H/HeN) mice. METHODS: The mice were exposed to 80% oxygen in a hyperoxic chamber for 0 (control), 48, or 96 h. After the exposure, bronchoalveolar lavage (BAL) was performed for differential cell counting and cytokine measurement. In lung homogenate, activation of NF-kappaB and STAT1 was also examined. RESULTS: In C3H/HeJ mice, hyperoxia-induced neutrophil accumulation in BAL fluid was significantly decreased compared with C3H/HeN. Hyperoxia for 96 h caused NF-kappaB translocation in C3H/HeN mice, which was significantly attenuated in C3H/HeJ mice (p < 0.05). In contrast, STAT1 activation occurred as early as after 48 h of oxygen exposure, which did not differ between the two strains. The levels of TNF-alpha, IL-6, and KC in BAL fluid were increased after oxygen exposure, which was suppressed by the lack of TLR4 signaling. CONCLUSION: These results suggest that TLR4-dependent NF-kB activation may be an important process of the upregulation of proinflammatory mediators and subsequent neutrophil accumulation into the lung during hyperoxia.

Limitation of cigarette consumption by CYP2A6*4, *7 and *9 polymorphisms.

The whole gene deletion CYP2A6*4, the defect of the main nicotine oxidase, contributes to limiting lifelong and daily cigarette consumption. However, the effects on smoking habits of CYP2A6*7 and *9, two major functional polymorphisms common in Asian populations, have not been reported. The present study examined the relationship between polymorphisms *4, *7 and *9 with the smoking habits of 200 Japanese smokers who visited the Keio University Hospital (Tokyo, Japan). The allele frequencies of *1 (wild type), *4, *7 and *9 were 52, 17, 11 and 20%, respectively. When the three polymorphisms were considered simultaneously, the percentages of homozygous wild type, heterozygote, and homozygous mutants and compound heterozygotes were 26.0, 52.5 and 21.5%, respectively. Homozygous mutants and compound heterozygotes (n = 43) smoked fewer cigarettes daily than heterozygotes (n = 105) and homozygous wild-type individuals (n = 52). Smokers with *7/*7, *9/*9 or *7/*9 had lower daily cigarette consumption than smokers with *1/*1. In conclusion, polymorphisms *4, *7 and *9 of CYP2A6 were detected in approximately three out of four Japanese smokers, and their daily cigarette consumption was genetically modulated by these functional polymorphisms.

Serum concentrations of high-mobility group box chromosomal protein 1 before and after exposure to the surgical stress of thoracic esophagectomy: a predictor of clinical course after surgery?

High-mobility group box chromosomal protein 1 (HMGB-1) has recently been shown as an important late mediator of endotoxin shock, intra-abdominal sepsis, and acute lung injury. However, its role in the systemic inflammatory response syndrome after major surgical stress, which may lead to multiple organ dysfunction syndrome, has not been thoroughly investigated. We hypothesized that serum HMGB-1 participates in the pathogenesis of postoperative organ system dysfunction after exposure to major surgical stress. A prospective clinical study was performed to consecutive patients (n = 24) with carcinoma of the thoracic esophagus who underwent transthoracic esophagectomy with three field lymph node resection between 1998 and 2003 at Keio University Hospital, Japan. Serum HMGB-1 concentrations were measured by enzyme-linked immunosorbent assay. Preoperative serum HMGB-1 levels correlated with postoperative duration of SIRS, mechanical ventilation, and intensive care unit stay. Three of the 24 patients had serious postoperative complications: sepsis in two, and acute lung injury in one. Serum HMGB-1 levels in patients without complications increased within the first 24 h postoperatively, remained high during postoperative days 2-3, and then decreased gradually by postoperative day 7. In patients with serious complications, serum HMGB-1 was significantly higher than that found in patients without postoperative complications at every time point except postoperative day 2. Preoperative serum HMGB-1 concentration seems to be an important predictor of the postoperative clinical course. Transthoracic esophagectomy induces an increase in HMGB-1 in serum even in patients without complications. Postoperative serum HMGB-1 concentrations were higher in patients who developed complications, and may be a predictive marker for complications in this setting.

Detection of mycobacteria in patients with pulmonary tuberculosis undergoing chemotherapy using MGIT and egg-based solid medium culture systems.

SETTING: National Minami-Yokohama Hospital, Kanagawa, Japan. OBJECTIVE: To compare the performance of a liquid medium system using the Mycobacteria Growth Indicator Tube (MGIT) with that of the conventional Japanese culture system using egg-based Ogawa medium, equivalent to Lowenstein-Jensen medium, in cases with pulmonary tuberculosis on chemotherapy. DESIGN: A single-centre prospective case study of 61 hospitalised patients from 1 May to 31 July 1998 on a standard 6-month regimen of anti-tuberculosis chemotherapy including isoniazid, rifampin, streptomycin or ethambutol, and pyrazinamide. Sputum cultures using both culture systems were performed bi-weekly up to week 16 of treatment, and were further monitored by MGIT alone at the end of chemotherapy and every 6 months after the end of chemotherapy up to 2 years. RESULTS: The detection time by MGIT gradually became longer with the progression of chemotherapy. The recovery rate at weeks 2, 4, 6, 8, and 10 by MGIT were significantly higher (P < 0.05) than on the Ogawa slants. Although one case was microbiologically diagnosed as a relapse, using the more sensitive MGIT system did not increase the relapse rate. CONCLUSION: The gradual prolongation of detection time with the progression of treatment and an attainment of negativity of sputum culture at 4 months after chemotherapy could be a useful intermediate marker to monitor the efficacy of treatment for patients with pulmonary tuberculosis by the MGIT system. Further evaluation is necessary to establish the utility of MGIT in monitoring the treatment process.

Usefulness of pulmonary vascular leakiness assessment in interstitial pneumonitis.

STUDY OBJECTIVE: Pulmonary vascular leakiness of (67)Ga-circulating transferrin in interstitial pneumonitis (IP) was estimated by our previously described method, and its ability to evaluate disease activity was compared with conventional (67)Ga scintigraphy. DESIGN: Using 30-min dynamic scanning data after IV injection of (67)Ga citrate, the exponential equilibration coefficient of (67)Ga between the intravascular and pulmonary interstitial compartments was calculated and defined as the leak index (LI). Pulmonary (67)Ga uptake was assessed by gallium index, determined by conventional static images taken 48 h after (67)Ga citrate injection. SETTING: Hospitalized patients. PARTICIPANTS: The study population consisted of 17 control patients and 20 patients with IP. RESULTS: The mean LI in patients with IP was significantly higher than in the control group (p < 0.0001), whereas no significant increase in gallium index was noted between the IP group and the control group. No significant correlation was found between gallium index and LI among all study participants. Mean LI in patients with active IP was significantly higher than in patients with stable IP (p = 0.0024). CONCLUSIONS: An increase in pulmonary vascular leakiness was found in patients with IP. LI may be useful to assess the disease activity.

New bronchoscopic microsample probe to measure the biochemical constituents in epithelial lining fluid of patients with acute respiratory distress syndrome.

OBJECTIVE: A noninvasive bronchoscopic microsampling (BMS) probe was developed to sample biochemical constituents of the epithelial lining fluid in small airways. DESIGN: Observational, controlled study. SETTING: Intensive care unit of academic medical center. PATIENTS AND PROCEDURE: BMS was applied in a control group of seven patients who had hemoptysis or small solitary peripheral nodules but no hypoxemia or other signs of acute inflammation and in four patients with acute respiratory distress syndrome (ARDS), to test whether BMS can ascertain the presence of acute pulmonary inflammation without complications. MEASUREMENTS AND RESULTS: Complications, including a significant decrease in arterial oxygen saturation, were observed neither during nor after BMS. In the ARDS group, albumin, lactate dehydrogenase, interleukin-6, basic fibroblast growth factor, and neutrophil elastase concentrations in epithelial lining fluid were significantly higher (p <.0001, p =.012, p <.0001, p <.0001, and p <.0001, respectively) than in the control group. Serial BMS was safely performed in one patient with ARDS, allowing us to observe a correlation between changes in the concentration of inflammation-related biochemical markers and clinical course of the disease. CONCLUSIONS: These results suggest that BMS is safe and useful to monitor pulmonary biochemical events in ARDS.

Pretreatment with FK506 improves survival rate and gas exchange in canine model of acute lung injury.

The novel effects of FK506 on shock induced by lipopolysaccharide and phorbol myristate acetate (LPS/PMA) were studied using beagles. Five groups were studied: endotoxin shock control group (both 0.5 mg/kg of LPS and 30 microg/kg of PMA, n = 6); methylprednisolone-treated endotoxin shock group (n = 5); FK506-treated endotoxin shock groups in which intravenous infusions of FK506 at 2.5 microg/kg/h (low dose, n = 5), 8 microg/kg/h (medium dose, n = 5), and 25 microg/kg/h (high dose, n = 5) were administered. In the control group, the survival rate was 33%. Also, arterial hypoxemia, systemic hypotension, and marked increases in pulmonary vascular resistance (PVR) and wet-to-dry weight ratio (W/D) were observed. FK506 treatment at both medium and high doses significantly attenuated these LPS/PMA-induced physiological changes, and the survival rates were 80 and 100%, respectively. On the other hand, in the methylprednisolone group, no obvious effects were observed. The present study suggests that FK506 could have prophylactic potential against acute lung injury in endotoxin shock.

Differential expression of CCR3 ligand mRNA in guinea pig lungs during allergen-induced inflammation.

OBJECTIVE AND DESIGN: The gene expression profile of CCR3 ligands, eotaxin, RANTES, and monocyte chemoattractant protein-3 (MCP-3), was examined in normal and inflamed guinea pig lungs. MATERIAL: Male Hartley guinea pigs (n = 49). METHODS: Pulmonary mRNA was obtained from naive animals, animals treated with intravenous lipopolysaccharide administration, and animals repeatedly exposed to aerosolized allergen (ovalbumin). Northern analysis was performed to quantify pulmonary expression of eotaxin, RANTES, and MCP-3 mRNA. Pulmonary eosinophil peroxidase (EPO) activity was measured to quantify eosinophil accumulation. RESULTS: Eotaxin and RANTES mRNAs, but not MCP-3 mRNA, were constitutively expressed in guinea pig lungs. Lipopolysaccharide treatment increased MCP-3 mRNA expression, but not eotaxin or RANTES mRNA. In contrast, allergen exposure in sensitized animals caused an increase in eotaxin mRNA, which demonstrated good temporal and quantitative correlation with pulmonary EPO activity, but not in MCP-3 or RANTES mRNA. CONCLUSIONS: Guinea pig CCR3 ligands demonstrated different gene expression profiles in normal and inflamed airways, suggesting that they play different physiological and pathophysiological roles in the airway.

Specific HLA in pulmonary MAC infection in a Japanese population.

Patients with pulmonary Mycobacterium avium complex (MAC) infection occasionally have neither past histories of pulmonary diseases nor underlying immunodeficiency conditions. Therefore, we hypothesized that MAC may be linked with a disease-susceptibility gene and determined human leukocyte-associated antigens (HLA) in patients with pulmonary MAC infection. HLA phenotypes were tested in 59 patients with pulmonary MAC infection, and diagnosed according to the criteria of the American Thoracic Society. Data of a Japanese population reported at the Tenth Japan HLA Workshop were used as a control. HLA-A33 (28.8% versus 12.5%, p = 5 x 10(-)(4)) and HLA-DR6 (50.8% versus 20.2%, p = 5 x 10(-)(8)) antigen frequencies in patients with MAC were significantly increased compared with those of the control population. Frequency of a haplotype A33-B44-DR6 in the MAC patients was also significantly increased compared with those of the control population (23.7% versus 4.2%; p = 3 x 10(-)(9)). These data suggest that development of pulmonary MAC infection is associated with specific HLA in a Japanese population.

Importance of interleukin-8 in the development of reexpansion lung injury in rabbits.

Reexpansion of a collapsed lung induces increased microvascular permeability leading to reexpansion pulmonary edema (REPE). This study was designed to prove the hypothesis that local overproduction of interleukin-8 (IL-8) induces inflammatory cell accumulation which leads to the induction of REPE. Initially, we examined the detailed characteristics of a rabbit model of REPE in association with IL-8 production and its mRNA expression. The lung tissue to plasma ratio of radiolabeled albumin (T/P ratio), the lung wet to dry ratio, and bronchoalveolar lavage (BAL) neutrophil counts were significantly increased in the reexpanded lung. IL-8 concentrations and mRNA expression were significantly increased in the reexpanded lung homogenate. Immunohistochemically, alveolar macrophages (AMs) and epithelial cells in the reexpanded lung and AMs in the collapsed lung were positive for IL-8. Second, we examined the effect of pretreatment with a specific monoclonal anti-IL-8 antibody (Ab) or control IgG on the development of REPE. The T/P ratio and BAL neutrophil counts were conspicuously decreased by pretreatment with anti-IL-8 Ab, but not with control IgG. On a histopathological study, lung injury and leukocyte infiltration were attenuated by the pretreatment with anti-IL-8 Ab. In conclusion, IL-8 production is enhanced in the reexpanded lung, and contributes to the development of REPE. The pretreatment with anti-IL-8 antibody may be useful as a novel protective therapy for this disease.

Attenuation of live E. coli-induced acute lung injury by X-ray irradiation in guinea pigs.

Irradiation is suspected to injure inflammatory cells, such as neutrophils and mononuclear phagocytes, cells known to contribute to the development of acute lung injury (ALI). This study examined whether preexposure to x-ray irradiation modifies ALI induced by E. coli injected intravenously in guinea pig. Thirty animals were divided into two control and two irradiated subgroups: the first control group received saline only (n = 8), and the second control group received E. coli, 2 x 10(9)/kg body weight, suspended in saline (n = 6), IV. The first irradiated group received a single 12-Gy dose + saline (n = 6), and the second irradiated group received a single 12-Gy dose + E. coli (n = 10). The lung wet-to-dry-weight ratio (W/D) and 125I-albumin lung tissue/plasma ratio (T/P) were measured as markers of lung injury. W/D was significantly higher in the control E. coli group than in the other groups. T/P in the control E. coli group was also increased compared with T/P measured in the other groups. In the control E. coli group, a marked increase in bronchoalveolar lavage (BAL) neutrophils was observed compared with the control saline group. However, no significant difference in BAL neutrophil counts was observed between the control and irradiated E. coli groups. In contrast, BAL macrophages were significantly reduced in the irradiated E. coli groups compared with the control E. coli group. These findings suggest that x-ray irradiation attenuates E. coli-induced ALI in guinea pigs, an effect explained, at least in part, by a reduction in the number of alveolar macrophages.

[Assessment of pulmonary epithelial permeability in interstitial lung diseases].

The pulmonary epithelial permeability of 99mTc-DTPA (diethylene triamine penta acetate) was assessed in patients with interstitial lung diseases including radiation pneumonitis, idiopathic interstitial pneumonia/pulmonary fibrosis, sarcoidosis, unclassified interstitial pneumonia, and in healthy subjects. Pulmonary epithelial permeability was estimated by the rate constant (kep) of inhaled 99mTc-DTPA clearance from the lungs. Healthy nonsmokers had a mean kep value of 0.82 +/- 0.26% min, and their kep values were constant irrespective of age or sex. Of healthy smokers, 53% showed an increase in kep. This increase correlated with their cigarette consumption per day, but was reversible after cessation of smoking. The provocative concentration of histamine to decrease FEV 1.0 by more than 20% caused an increase in epithelial permeability. However, its effect on permeability was transient, limited, and not dose-dependent. During lung inflation by continuous external negative pressure or by positive end-expiratory pressure, pulmonary 99mTc-DTPA clearance was increased, suggesting changes in epithelial permeability. The patients with diffuse interstitial lung diseases also showed increased permeability compared with healthy nonsmokers. In the patients with pre-existing radiation pneumonitis, the mean kep value obtained from the area with infiltration on chest X-ray films was significantly higher than that from the opposite lung. In the prospective study, 3 of 11 patients developed radiation pneumonitis during the course of radiation therapy. The mean kep value obtained in the 3 patients who developed radiation pneumonitis increased just before onset, and further increased when the disease manifested clinically. We believe that 99mTc-DTPA aerosol inhalation is a sensitive test for the detection of inflammatory changes in the bronchioalveolar epithelium.

Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection.

The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.

Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.

We report a girl with oral, facial, and digital anomalies including multiple alveolar frenula, lobulated tongue with nodules, a posterior cleft palate, hypertelorism, a prominent forehead with a large anterior fontanelle, and postaxial polydactyly in both hands and the right foot, features compatible with the oral-facial-digital syndrome (OFDS). In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker malformation and retrobulbar cysts were observed on MRI. These additional malformations have not been reported in OFDS type IX. The frequent apnoeic spells which occurred immediately after birth were relieved after cystoperitoneal shunt implantation for hydrocephalus. Considering our case and previous reports of OFDS type IX, including two male sibs, a boy born to consanguineous parents, and three females, inheritance is probably autosomal recessive.

Downmodulation of IL-8 receptors, type A and type B, on human lung neutrophils in vivo.

We examined the expression of interleukin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8-RB), on peripheral blood and bronchoalveolar lavage (BAL) fluid neutrophils; we also examined IL-8 and other chemoattractants in the epithelial lining fluid (ELF) of patients with chronic lower respiratory tract infection (CLI) to elucidate the in vivo regulation of IL-8Rs. Neutrophils were stained with monoclonal antibodies specific for IL-8-RA and IL-8-RB. We detected higher levels of IL-8 (81.6 +/- 25.4 ng/ml, mean +/- SE), leukotriene (LT) B4, and IL-1 beta in the ELF of the CLI patients than in their serum (P < 0.05). The expression of IL-8Rs on BAL neutrophils was significantly lower than that on peripheral blood neutrophils (P < 0.01 for both). In vitro analysis showed that low-level IL-8 (50 ng/ml) alone did not affect IL-8R expression but that it was downregulated by high-level IL-8 (500 ng/ml) alone and by low-level IL-8 in combination with LTB4 or IL-1 beta. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-1 beta but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL-8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.

[Spinal cord ischemia caused by dissecting aortic aneurysm in a patient with acute exacerbation of pulmonary emphysema].

A 61-year-old man with pulmonary emphysema was admitted due to acute exacerbation of chronic respiratory failure and a complaint of chest pain. A chest CT scan on admission showed aneurysmal dissection from the ascending aorta to the descending aorta. Analgesia was noted below the fourth thoracic vertebra, which supplies the accessory respiratory muscles including the intercostal muscles. Even after recovery from circulatory failure, his chest muscles were weak and he could not be removed from mechanical ventilation. An autopsy revealed ischemia of the spinal cord at the T4 level. In contrast, The C3 level of the spinal cord, which supplies the diaphragm, was intact. Paralysis of accessory respiratory muscles including intercostal muscles may have caused the continuation of the respiratory failure. This case shows the importance of accessory respiratory muscles in maintaining chest wall movement in patients with chronic pulmonary emphysema.